Organic acids of the diphenylmethane series and a process of preparing



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i Patented May 2, 19 33 I i IVANEGUBELMAITN, HENRY .r.w1i:II.'ANn, ANDo'rTo s'r ALLMANN, OFSOUTHK'LMIL WAUKEE, WISCONSIN, AssIeNoRs, BY MESNEASSIGNMENTS, T0 I. DU PONT DE EmoURs & COMPANY, A CORPORATION orDELAWARE:

ORGANIC ACIDS OF THE, DIPHNNYLMETHAN SERIES AND a process of preparingthese bodies-bythe halogenation of the corresponding 3-aminoandnitrogensubstituted 3-amino-4 substi{ tuted' benzyl ortho benzoic acids.

It is an object of this inventionto provide a method wherebytheseproducts may be made technically available, as they are valu- 7 Ohmnin0 4 ch10r0 6, am o t bellzyl ableproducts inthemselves and moreparticularly so in connection "with the manufacture of dyestufis.

Otherand further important objects of this invention will becomeapparent from the following description and appended claims.

The 'bodiesto which this invention relates have the following generalconstitution as the phthaloyl residue, or whereiniR stands for hydrogenwhile B stands for an acidyl radical suchas acetyl, benzoyl,toluenesulfonyl, the group 1 R h'aving thefsa me significance as below,the compoundin this case being a substituted A rnoonss or ranmam,

Application. filed January: 2,1929; Serial No. 329,946. I

urea), and similar groups; wherein R? is a hydrogen, methyl, methoxy,ethoxy, halogen, carboxyl, sulfonic acid and the like, and

halogen is a chlorine or; bromineatom."

f Among the products which we include in our invention are the followingand their acidyl nitrogen substituted derivatives:

3-amino-4-methoXy-6-bron o ortho benzyl benzoic acid benzoic acidbenzoic acid 37-amino-4-methoxy-6 -chloro flortho benzyl' J benzoicacid3raminoleethoxy-6-bromo benzoic acid 1 3-amino+4-methyl-6-chloro,benzoic acid ortho .liyenzyl;

benzoic acid The f-position maybe substituted by other groups and theabove list is given merely to illustrate the type of compounds referredto.

e have found that the 3 amino-4f-suhstituted benzyl benzoic acids, whichare the subjects of our copending applications, Serial N os.290,027and290,028,' filed July 2nd, 1928, may bereadily halogenated usingmethods adapted for the halogenation of similar aniline derivatives.Thehalogen forthe most part enters the para position tothe amino' group. In the halogenation of these bodies, I

' we prefer to useas starting material an acidyl derivative, as forexample, an acetyl-amino The (Y-halogen acetyl amino bodies thusobtained may then behydrolyz'ed to the"3' j amino-6 h alogen benzyl vbenzoici acids by generally known methods adapted to similar compoundsor they maybe used as such for the-preparation of othercompoundssuitable for dyestuifs. g v I Inflth'e preparation ofsome of'the acidylderivatives, it is more practical to start; with the halogenated aminesobtained from the ac'etyl-aminoid'-suhstituted bodies. by hy- 1 3amino-4methyl-6ebroino r; .ortho b to" drolysis and treat them with variousacidylating agents as for example, phthalic anhydride, phosgene, benzoylchloride and the like, by known methods adapted for the prep aration ofother acidyl amino bodies.

The halogenation may be performed in a variety of ways and in itspreferred form depends largely upon the individual starting materialemployed. In the chlorination we employ either chlorine as such, or achlorinating agent, such as sulfuryl chloride, SO CI The chlorinationmay also be effected by the tions, but practically insoluble in water.

They can be hydrolyzed to the 3-amino-4- substituted -6-halogen benzylbenzoic acids, which in physical properties resemble the unhydrolyzedbodies. These bodies may be condensed with suitable condensing agents tothe corresponding anthrones which upon oxidation give the correspondinganthraquinones. The anthraquinones produced thereby are thel-aminol-l1alogen-2-substituted anthraquinones, the importance of thelatter being well known. 7

To illustrate the preferred embodiments of our invention the followingexamples are given. The proportions are in parts by weight.

I ortho benzoic acid, which may be prepared Example I 50 parts of3-a1nino-4-methoxy benzyl by reducing 3-amino-4- 1nethoxy benzoyl orthobenzoic acid with zinc dust and ammonia, are added to 150 parts ofglacial acetic acid. There are then added 50 parts of acetic anhydrideand the mixture is heated tothe boiling point for ten minutes. 12 partsof water are added and the mixture cooled to about 25- C. parts ofbromine in parts o facetic acid are now added over a period of may berecrystallized from acetic acid and then has a melting point of 228 to229 C.

about one hour. The 3-acetyl amino-4- methoxy-6-bromo benzyl orthobenzoic acid crystallizes out and is filtered off. It is washed with alittle acetic acid and dried. It

Upon hydrolyzing this compound withdiluted caustic soda the8-amino-4-methoxy-6- bromo benzyl ortho. benzoic acid can be obtained.The latter body has a melting point of 189190 C.

E sample [I 50 parts of 3-amino4' chloro benzyl ortho benzoic acid,which may be obtained by reducing'3-amino-4-chloro benzoyl ortho benzoicacid with zinc dust and ammonia, are added to 200 parts of glacialacetic acid and 50 parts of acetic anhydride. The mixture is heated toreflux temperaturesior a;' short time. It is then cooled to 90-100 C.and there are then added over a period of one hour 30 parts of sulfurylchloride, SO Gl The mixture is cooled to room temperature and filtered.The product is washed with a little acetic acid and dried. Afterrecrystallizing from acetic acid, the product 3-acetyl-amino- 4,6-dichloro benzyl ortho benzoic acid has a melting point of 2l62l7 C. Itcan be hydrolyzed to the free base of melting point 164-165 C.

EwampZe H I 3-amino-4-methoxy-benzyl-ortho-benzoic acid can behalogenated as in Example 1, except that instead of using bromine,chlorine is'used. The 3-acetyl-aminol-methoxy-6- chloro-benzyl orthobenzoic acid has a melting point of 226 C. Upon hydrolyzing'this productthere is obtained a base of melting point 190 0.

Example I V 3-aminol-methoxy benzyl ortho benzoic acid can bechlorinated as in Example III, except using as starting material3-amino-4- methoxy benzyl benzoic acid in the place of 3- amino 4methoxybenzyl ortho benzoic acid. The 3'-acetyl-amino-4-ethoxy-6-chl0ro benzylortho benzoic acid melts at 219-220 C.

Ewample V parts of 3-amino-4c-methyl benzyl ortho benzoic acid (meltingpoint 157 (1.), which may be prepared by reducing 3- an1ino-4-methylbenzoyl ortho benzoic acid with zinc dust and ammonia, are added to 150parts of glacial acetic acid and 50 parts of acetic anhydride. This massis heated to reflux temperatures for 10 minutes. 20 parts of Water and500 parts of glacial acetic acid are then added, and at a temperature of90-100 C. over a period of 1 to 2 hours, 45 parts of bromine in 50 partsof glacial acetic acid. The mass is cooled to room temperature, filteredand the filter cake washed with a little glacial acetic acid. Themelting point of 3- acetyl amino 1. methyl 6- bromo benzyl ortho benzoicacid is 246 C. Upon hydrolysis the acetyl body is transformed. into abase of melting point 193-194 C.

I ortho benzoic acid are added to 150 parts of glacial acetic acid and50 parts of acetic 'anhydride. The mass is refluxed for about 10 minutesand cooled to 90-100"; C. 300 parts of glacial acetic acid are nowadded, and at 90100 0., 35 parts of sulfuryl chloride (SO CI are addedover a period of 1 to 2 hours. The mass is cooled to room tempera- Thefilter cake is washed ture and filtered. with a small amount of aceticacid and dried. The melting point of 3-acetyl-amino-4- methyl-6-chlorobenzyl benzoic acid is. 256

C. Upon. hydrolysis a base is obtained having a melting point of 19649?C. I

7 Emample VI] Into 200 parts of nitrobenzene are added 50 parts of3-amino4 methoXy-6 chloro benzyl ortho benzoic acid as. obtained inExample III and 50 parts of phthalic anhydride. The mixture is heated tothe boiling point and distilled until free of water. It is then cooledto room temperature, whereupon the phthaloyl body crystallizes out. 100

parts of alcohol are now added and the prod uct is filtered off, washedwith a small amount of alcohol to free the body of nitrobenzene. Theproduct can be easily crystallized from nitrobenzene or glacial. aceticacid in the form of white crystals;

Emample VIII i To 400 parts of water are added 50 parts ofp-toluene-sulfon-chloride. The mixture is heated to to C. and there isadded sufiicient caustic soda solutionto give a weak alkalinity onbrilliant yellow paper. To this mixture isthen added over a periodof onehour a solution of the sodium saltof 3 amino-4-methyl-6-chl0ro benzylortho benzoic acid containing-fiO parts of the latter tained can berecrystallized from. glacial acetic acid in the form of white crystals.

; Ewamplc IX T0400 parts of water add50 parts of 3'-am-inO-P-methyl-G'-chloro benzyl ortho benzoic acid as prepared inExample VI and just sufiicient' caustic soda solution. to give analkaline test on brilliant yellow paper. Now

' add to this solution at a temperature of 20- 25 C. 50 parts of benzoylchloride and just suificient caustic soda solution to maintain a :slightalkalinity of the solution and allow to with a mineral acid and -.filteroff the precipitated body. 3-benzoyl-amino-4-methyl- 6-chloro-benzylortho benzoic acid as thus obtained is a white powder. It can berecrystallized from alcohol in the form of white crystals. i

We are aware of the, fact that instead of using the acetyl derivativesfor the preparation of these bodies, other nitrogensubstitutedderivatives, as for example benzoyl, toluene sulfonyl,carbonyl-amino-benzylortho-benzoic acid, phthaloyl and the like may beemployed. Similarly we are: aware that other solvents may be used, asfor exreact about hour. Acidify the solution ample, nitrobenzene andother halogenating, agents. The improvement residing 1n this n ventionis in the fact that practically all the halogen introduced into themolecule enters in the 6-position, thereby producing compounds whichafter condensation and oxidation are valuable anthraquinone'derivatives. This rule fails but in rare cases. Y I

Inthe claims where the term an amino? or a 3-amino is used, we mean toinclude both free amino and acidyl amino groups, and wherein the termfacidyl is used we means toinclude both radicals of monobasic anddibasic organic acids.

. We are aware that numerous details of the process may be variedthrough a Wide range without departing from the principles of thisinvention, and we, therefore, do not purpose limiting the patent grantedhereonotherwise than necessitated by the prior art.

We claim as our invention:

1.. The process which comprises treating with halogenating agents in'thepresence of a protecting agent for any free amino groups abenzyl-ortho-benzoic acid being substituted in the 3- position by anamino group of the yp r o R RI with ahalogenating agent...

3. The process which comprises reacting 3'-acidyl-amino-ortho-benzylbenzoic acids 1n the presence of a solvent with a halogenating-agent.

4. .The process" which "comprises halogenat, ing inthe presenceof-acetic acid 3"-acetylamino-benzyl-ortho-benzoic acids substituted inthe 4 position with a member of the groups consisting of alykyl, alkoxy,v halogen, "carboXyl, and sulfonic acid group, and hydrolyz--- ingtheproduct. e

COOH

wherein R and R represent two hydrogen atoms, one hydrogen atom and anacidyl group, or the diacyl radical of a diabasic organic acid; Hrepresents a member of the group consisting of alkyl, alkoxy, halogen,carboxyl and sulfonic acid groups, and halogen stands for a chlorine orbromine atom.

6. As new articles of manufacture, 3- acidyl-amino 6-halogen benzylortho benzoic acids substituted in the 4-position with a member of thegroup consisting of alkyl, al.-

koXy, halogen, carboxyl, and sulfonic acid groups.

7. The process which comprises heating a 3-amino-benzyl-ortho-benzoicacid substituted in the 4J-position with a member of the groupconsisting of alkyl, alkoxy, halogen, carboXyl, and sulfonic acid groupsin the presence of a protecting agent for the amino group, cooling thesolution, slowly adding thereto a halogenating agent and filtering theresulting precipitate.

8. The process which comprises heating a 3-amino-benzyl-ortho-benzoicacid substituted in the F-position with a member of the group consistingof alkyl, aikoxy, halogen, carboxyl, and sulfonic acid groups in thepresence of acetic acid, cooling the solution, slowly adding thereto ahalogenating and filtering the resulting precipitate.

9. The process which comprises heating a 3-amino-benzyl-ortho-benzoicacid substituted in the l'-position with a member of the groupconsisting of alkyl, alkoxy, halogen, carbonyl, and sulfonic acid groupsand acetic acid to boiling, cooling the solution to approximately roomtemperatures, slowly adding thereto a halogenating agent and filteringthe resulting precipitate.

10. The process of preparing a 3-acetyl- -amino 6 chlorobenzyl-ortho-benzoic acid substituted in the 4l-position with a memberof the group consisting of alkyl, alkoxy, halogen, carboxyl, andsulfo-nic acid groups which comprises treating a,3'-acetyl-amino-4-sub--stituted-benzyl-ortho-benzoic acid with a chlorinating agent.

11. The process of. forming3-acetylaminolalkoXy-(i'-chloro-benZyl-ortho-benzoic acid whichcomprises treating 3-acetylamino 4 alkoxy-benzyl-ortho-benzoic acid witha chlorinating agent at approximately room temperatures.

12. As new articles of manufacture, bodies of the following formula:

COOH

wherein R and R represent two hydrogen atoms, one hydrogen atom and anacetyl group, or the diacyl radical of a dibasic organic acid and Rrepresents a member of the group consisting of alkyl, alkoXy, halogen,carboxyl and sulfonic acid groups.

13. As new articles of manufacture, bodies of the following formula:

COOH

wherein R and R represent acetyl groups and R a member of the groupconsisting of alkyl, alkoxy, halogen, carboxyl and sulfonic acid groups.

14:. As new articles of manufacture, 3'- acetyl-amino-6-chloro benzylortho-benzoic acids substituted in the l--position by a member of thegroup consisting of alkyl, alkoxy, halogen, carboxyl and sulfonic acidgroups.

15. As new articles of manufacture, 3- acidyl-amino -alkoxy-6 halogenbenzylortho-benzoic acids.

16. As new articles of manufacture, 3 acetyl-amino-4J- alkoxy 6- halogenorthobenZyLbenzoic acids.

17. As new articles of manufacture, 3- acetyl-amino-4J-alkoXy-6-chloro-."benzyl sortlio-bensoic acids.

In testimony whereof, we have hereunto subscribed our names atCarrollville, Milwaukee County, Wisconsin.

IVAN GUBELMANN. HENRY J. WVEILAND. OTTO STALLMANN.

